Using baseline data from the PrEP1519 cohort, in this article we aimed to analyze: (i) the effectiveness of demand creation strategies (DCS) to enroll adolescent men who have sex with men (AMSM) and adolescent transgender women (ATGW) into an HIV combination prevention study in Brazil; (ii) the predictors of DCS for adolescents' enrollment; and (iii) the factors associated with DCS by comparing online and face-to-face strategies for enrollment. The DCS included peer recruitment (i.e., online and face-to-face) and referrals from health services and non-governmental organizations (NGOs). AMSM and ATGW who agreed to participate in the study could opt to enroll in either PrEP (PrEP arm) or to use other prevention methods (non-PrEP arm). Bivariate and multivariate analyses were conducted and logistic regression odds ratios were estimated. The DCS reached 4529 AMSM and ATGW, the majority of which were derived online (73.8%). Of this total, 935 (20.6%) enrolled to participate (76.6% in PrEP arm and 23.4% in non-PrEP arm). The effectiveness of enrolling adolescents into both arms was greater via direct referrals (235/382 and 84/382, respectively) and face-to-face peer recruitment (139/670 and 35/670, respectively) than online (328/3342). We found that a combination under DCS was required for successful enrollment in PrEP, with online strategies majorly tending to enroll adolescents of a higher socioeconomic status. Our findings reinforce the need for DCS that actively reaches out to all adolescents at the greatest risk for HIV infection, irrespective of their socioeconomic status.